INHIBITION OF MAMMALIAN NITRIC-OXIDE SYNTHASES BY AGMATINE, AN ENDOGENOUS POLYAMINE FORMED BY DECARBOXYLATION OF ARGININE

Agmatine, decarboxylated arginine, is a metabolic product of mammalian cells. Considering the close structural similarity between L-arginine and agmatine, we investigated the interaction of agmatine and nitric oxide synthases (NOSs), which use L-arginine to generate nitric oxide (NO) and citrulline. Brain, macrophages and endothelial cells were res pectively used as sources for NOS isoforms I, II and III. Enzyme activ ity was measured by the production of nitrites or L-citrulline. Agmati ne was a competitive NOS inhibitor but not an NO precursor. K-i values were approx. 660 mu M (NOS I), 220 mu M (NOS II) and 7.5 mM (NOS III) . Structurally related polyamines did not inhibit NOS activity. Agmati ne, therefore, may be an endogenous regulator of NO production in mamm als.